Hydrochloric Acid → HCID 66665927, compound

HRID 872347Notes

Reaction equation

HRID 872347 reaction equation
C(OC(=O)[NH:7][C:8]1([C:12]2[CH:17]=[CH:16][C:15]([C:18]3[N:19]=[C:20]4[CH:25]=[C:24]([C:26]5[CH:31]=[CH:30][N:29]=[CH:28][CH:27]=5)[CH:23]=[CH:22][N:21]4[C:32]=3[C:33]3[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=3)=[CH:14][CH:13]=2)[CH2:11][CH2:10][CH2:9]1)(C)(C)C.Cl.O1CCOCC1>CO.C(Cl)Cl>[C:33]1([C:32]2[N:21]3[CH:22]=[CH:23][C:24]([C:26]4[CH:27]=[CH:28][N:29]=[CH:30][CH:31]=4)=[CH:25][C:20]3=[N:19][C:18]=2[C:15]2[CH:14]=[CH:13][C:12]([C:8]3([NH2:7])[CH2:11][CH2:10][CH2:9]3)=[CH:17][CH:16]=2)[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 86691042HCID 86691042, compound

Product 1

HCID 66665927HCID 66665927, compoundYield 83%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of {1-[4-(3-phenyl-7-pyridin-4-yl-imidazo[1,2-a]pyridin-2-yl)-phenyl]-cyclobutyl}-carbamic acid tert-butyl ester (60 mg, 0.12 mmol) in MeOH (0.5 mL) and CH2Cl2 (0.7 mL) was added a 4 molar solution of HCl in dioxane (0.6 mL, 2.3 mmol, 20 equiv) and the resulting solution was stirred at room temperature for 12 h. The resulting solution was added to ice water, and the resulting mixture was extracted with CH2Cl2 (3×25 mL). The combined organic phases were dried (Na2SO4 anh), and concentrated under reduced pressure. The remaining material was purified using MPLC (Biotage Isolera Flash NH2 Snap 10 reverse phase column; 100% CH2Cl2 for 4 min., gradient to 95% CH2Cl2: 5% MeOH over 1 min.; 95% CH2Cl2: 5% MeOH for 2.5 min., gradient to 90% CH2Cl2: 10% MeOH over 1 min., 90% CH2Cl2: 10% MeOH for 2.5 min., gradient to 80% CH2Cl2: 20% MeOH over 1.5 min., 80% CH2Cl2: 20% MeOH for 0.8 min., gradient to 74% CH2Cl2: 26% MeOH over 2.2 min., gradient to 70% CH2Cl2: 30% MeOH over 1.8 min., 70% CH2Cl2: 30% MeOH for 7.4 min.) to give 1-[4-(3-phenyl-7-pyridin-4-yl-imidazo[1,2-a]pyridin-2-yl)-phenyl]-cyclobutylamine (40 mg, 83%): UPLC-MS (Method 2): RT=1.22 min; m/z (rel intensity) 417 (700, (M+H)+), 833 (40, (2M+H)+).

Workup

  1. extractionthe resulting mixture was extracted with CH2Cl2 (3×25 mL)
  2. dry with materialThe combined organic phases were dried (Na2SO4 anh)
  3. concentrationconcentrated under reduced pressure
  4. customThe remaining material was purified
  5. wait100% CH2Cl2 for 4 min.
  6. waitgradient to 95% CH2Cl2: 5% MeOH over 1 min.
  7. wait95% CH2Cl2: 5% MeOH for 2.5 min.
  8. waitgradient to 90% CH2Cl2: 10% MeOH over 1 min.
  9. wait90% CH2Cl2: 10% MeOH for 2.5 min.
  10. waitgradient to 80% CH2Cl2: 20% MeOH over 1.5 min.
  11. wait80% CH2Cl2: 20% MeOH for 0.8 min.
  12. waitgradient to 74% CH2Cl2: 26% MeOH over 2.2 min.
  13. waitgradient to 70% CH2Cl2: 30% MeOH over 1.8 min.

Sources & evidence

ORD record
ord-1438ea97208e4cb490f1a196cdfecea7
Source dataset
uspto-grants-2015_03
Patent number
US08975265B2

Reaction notes

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